Dynamics of seeded Aβ40-fibril growth from atomistic molecular dynamics simulations: kinetic trapping and reduced water mobility in the locking step

Filamentous β-amyloid aggregates are crucial for the pathology of Alzheimer's disease. Despite the tremendous biomedical importance, the molecular pathway of growth propagation is not completely understood and remains challenging to investigate by simulations due to the long time scales involved. Here, we apply extensive all-atom molecular dynamics simulations in explicit water to obtain free energy profiles and kinetic information from position-dependent diffusion profiles for three different Aβ9-40-growth processes: fibril elongation by single monomers at the structurally unequal filament tips and association of larger filament fragments. Our approach provides insight into the molecular steps of the kinetic pathway and allows close agreement with experimental binding free energies and macroscopic growth rates. Water plays a decisive role, and solvent entropy is identified as the main driving force for assembly. Fibril growth is disfavored energetically due to cancellation of direct peptide-peptide interactions and solvation effects. The kinetics of growth is consistent with the characteristic dock/lock mechanism, and docking is at least 2 orders of magnitude faster. During initial docking, interactions are mediated by transient non-native hydrogen bonds, which efficiently catch the incoming monomer or fragment already at separations of about 3 nm. In subsequent locking, the dynamics is much slower due to formation of kinetically trapped conformations caused by long-lived non-native hydrogen bonds. Fibril growth additionally requires collective motion of water molecules to create a dry binding interface. Fibril growth is further retarded due to reduced mobility of the involved hydration water, evident from a 2-fold reduction of the diffusion coefficient

Meteorologic parameters analysis above Dome C made with ECMWF data

In this paper we present the characterization of all the principal meteorological parameters (wind speed and direction, pressure, absolute and potential temperature) extended over 25 km from the ground and over two years (2003 and 2004) above the Antarctic site of Dome C. The data set is composed by 'analyses' provided by the General Circulation Model (GCM) of the European Center for Medium Weather Forecasts (ECMWF) and they are part of the catalog MARS. A monthly and seasonal (summer and winter time) statistical analysis of the results is presented. The Richardson number is calculated for each month of the year over 25 km to study the stability/instability of the atmosphere. This permits us to trace a map indicating where and when the optical turbulence has the highest probability to be triggered on the whole troposphere, tropopause and stratosphere. We finally try to predict the best expected isoplanatic angle and wavefront coherence time employing the Richardson number maps, the wind speed profiles and simple analytical models of CN2 vertical profiles.Comment: 28 pages, 14 figures, pdf file, to be published on July 2006 - PASP, see also http://www.arcetri.astro.it/~masciad

Nonlocal mechanism for cluster synchronization in neural circuits

The interplay between the topology of cortical circuits and synchronized activity modes in distinct cortical areas is a key enigma in neuroscience. We present a new nonlocal mechanism governing the periodic activity mode: the greatest common divisor (GCD) of network loops. For a stimulus to one node, the network splits into GCD-clusters in which cluster neurons are in zero-lag synchronization. For complex external stimuli, the number of clusters can be any common divisor. The synchronized mode and the transients to synchronization pinpoint the type of external stimuli. The findings, supported by an information mixing argument and simulations of Hodgkin Huxley population dynamic networks with unidirectional connectivity and synaptic noise, call for reexamining sources of correlated activity in cortex and shorter information processing time scales.Comment: 8 pges, 6 figure

Action-derived molecular dynamics in the study of rare events

We present a practical method to generate classical trajectories with fixed initial and final boundary conditions. Our method is based on the minimization of a suitably defined discretized action. The method finds its most natural application in the study of rare events. Its capabilities are illustrated by non-trivial examples. The algorithm lends itself to straightforward parallelization, and when combined with molecular dynamics (MD) it promises to offer a powerful tool for the study of chemical reactions.Comment: 7 Pages, 4 Figures (3 in color), submitted to Phys. Rev. Let

Network equilibration and first-principles liquid water.

Motivated by the very low diffusivity recently found in ab initio simulations of liquid water, we have studied its dependence with temperature, system size, and duration of the simulations. We use ab initio molecular dynamics (AIMD), following the Born-Oppenheimer forces obtained from density-functional theory (DFT). The linear-scaling capability of our method allows the consideration of larger system sizes (up to 128 molecules in this study), even if the main emphasis of this work is in the time scale. We obtain diffusivities that are substantially lower than the experimental values, in agreement with recent findings using similar methods. A fairly good agreement with D(T) experiments is obtained if the simulation temperature is scaled down by approximately 20%. It is still an open question whether the deviation is due to the limited accuracy of present density functionals or to quantum fluctuations, but neither technical approximations (basis set, localization for linear scaling) nor the system size (down to 32 molecules) deteriorate the DFT description in an appreciable way. We find that the need for long equilibration times is consequence of the slow process of rearranging the H-bond network (at least 20 ps at AIMDs room temperature). The diffusivity is observed to be very directly linked to network imperfection. This link does not appear an artifact of the simulations, but a genuine property of liquid water

Morphology and time variability of Io's visible aurora

Clear-filter imaging of Io during the Galileo nominal and extended missions recorded diffuse auroral emissions in 16 distinct observations taken during 14 separate eclipses over a two year period. These images show that the morphology and time variability of the visible aurora have several similarities to Io's far ultraviolet emissions. The orbital leading hemisphere of Io is consistently brighter than the trailing hemisphere, probably due to a greater concentration of torus electrons in the wake region of the satellite. The locations of the polar limb glow and the bright equatorial glows appear to correlate with Io's System III longitude. Unlike the far ultraviolet emissions, the visible aurorae are enhanced near actively venting volcanic plumes, probably because of molecular emission by SO_2

Lucky Imaging survey for southern M dwarf binaries

While M dwarfs are the most abundant stars in the Milky Way, there is still large uncertainty about their basic physical properties (mass, luminosity, radius, etc.) as well as their formation environment. Precise knowledge of multiplicity characteristics and how they change in this transitional mass region, between Sun-like stars on the one side and very low mass stars and brown dwarfs on the other, provide constraints on low mass star and brown dwarf formation. In the largest M dwarf binary survey to date, we search for companions to active, and thus preferentially young, M dwarfs in the solar neighbourhood. We study their binary/multiple properties, such as the multiplicity frequency and distributions of mass ratio and separation, and identify short period visual binaries, for which orbital parameters and hence dynamical mass estimates can be derived in the near future. The observations are carried out in the SDSS i' and z' band using the Lucky Imaging camera AstraLux Sur at the ESO 3.5 m New Technology Telescope. In the first part of the survey, we observed 124 M dwarfs of integrated spectral types M0-M6 and identified 34 new and 17 previously known companions to 44 stars. We derived relative astrometry and component photometry for these systems. More than half of the binaries have separations smaller than 1 arcsec and would have been missed in a simply seeing-limited survey. Correcting our sample for selection effects yields a multiplicity fraction of 32+/-6% for 108 M dwarfs within 52 pc and with angular separations of 0.1-6.0 arcsec, corresponding to projected separation 3-180 AU at median distance 30 pc. Compared to early-type M dwarfs (M>0.3M_Sun), later type (and hence lower mass) M dwarf binaries appear to have closer separations, and more similar masses.Comment: 18 pages, 9 figures. Minor corrections and changes. Revised to match accepted A&A versio